Hydrochloric Acid → HCID 58292678, compound

HRID 1798206Notes

Reaction equation

HRID 1798206 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20](Cl)[N:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2].[C:26]([O:30][C:31](=[O:37])[NH:32][CH2:33][CH2:34][CH2:35][OH:36])([CH3:29])([CH3:28])[CH3:27].[H-].[Na+].[NH4+].[Cl-].Cl>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20]([O:36][CH2:35][CH2:34][CH2:33][NH:32][C:31]([O:30][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:37])[N:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 3838134tert-butyl N-(3-hydroxypropyl)carbamateHCID 58292555HCID 58292555, compound

Product 1

HCID 58292678HCID 58292678, compoundYield 65.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [6-(2-chloro-pyrimidin-4-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (0.5 g, 1.37 mmol) and (3-hydroxy-propyl)-carbamic acid tert-butyl ester (0.48 g, 2.75 mmol) in DMF at 0° C. was added NaH (0.2 g, 4.13 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 12 hours. Saturated NH4Cl (10 mL) was added at 0° C. and the solution acidified to pH˜5 with dilute HCl. The mixture was extracted with EtOAc (2×10 mL) and the organic extracts washed with water (10 mL), dried and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (DCM:MeOH 95:5) to give {6-[2-(3-tert-butoxycarbonylamino-propoxy)-pyrimidin-4-yloxy]-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl}-acetic acid ethyl ester (0.45 g, 65%). 1H NMR (400 MHz, DMSO): δ 9.10 (s, 1H), 8.41 (d, J=5.2 Hz, 1H), 8.22 (d, J=5.6 Hz, 1H), 7.24 (s, 1H), 7.09 (s, 1H), 5.51 (d, J=9.6 Hz, 1H), 4.02 (q, J=7.2 Hz, 2H), 3.93 (t, J=6.0 Hz, 2H), 3.07-3.02 (m, 3H), 2.28-2.27 (m, 1H), 2.26 (s, 3H), 1.77 (t, J=6.4 Hz, 2H), 1.33 (s, 12H), 1.11 (t, J=6.8 Hz, 3H). MS (ESI) m/z=502 [M+H]+.

Workup

  1. extractionThe mixture was extracted with EtOAc (2×10 mL)
  2. washthe organic extracts washed with water (10 mL)
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel flash column chromatography (DCM:MeOH 95:5)

Sources & evidence

ORD record
ord-4676c4b32eb24bb5aca5f85d28920083
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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